Neuronal migration is an essential process during neural development that delivers neurons to programmed locations to participate in critical circuit operations. Adult neurogenesis of the hippocampus preserves a full developmental process from neuronal birth to circuit integration and displays features of radial and tangential migration, commonly seen in development. However, the circuitry and molecular mechanisms that initiate and execute migration in adult neurogenesis remain poorly understood. Recently, I discovered tangential migratory behavior of the proliferating neuroblast stage of neurogenesis, which is modulated by environmental enrichment in vivo. These findings have provided a new entry point for determining the stereotypical behaviors and regulation of neuroblast migration by activity. This proposal is focused on identifying key components of neuronal activity-dependent signaling and intracellular signal transduction that guide a newborn neuroblast and which may lead to disrupted neuronal positioning if dysregulated. The proposal uses a novel in vivo imaging platform (i) combined with cell-type specific chemogenetics to test the activity-dependent regulatory factors of neuroblast migration and (ii) combined with RNAi based approaches to identify intrinsic factors of neuroblasts that critically regulate migration. I expec the results to determine the contribution of these regulatory components to physiological neuroblast migration, and discern if loss of these components have associated pathologies. These studies will identify novel mechanisms regulating neuronal migration in the adult hippocampus, elucidating unique neuroplasticity regulation that has broad translational value. Finally, this proposal will teach me critically in research practice, ethical research conduct and scientific communication for the duration of my graduate training.